MAPK8 and thoracic aortic aneurysm: Loss of SMAD4, a canonical TGF-β pathway mediator, has been shown to exacerbate the progression of thoracic aortic aneurysm and dissection in mouse MFS models, whereas inhibition of non-canonical TGF-β signaling, mediated through ERK, JNK, and p38, has been shown to protect against progression of thoracic aortic disease [53].